Satiety does not affect gustatory activity in the nucleus of the solitary tract of the alert monkey

Feeding to satiety decreases the acceptability of the taste of food. In order to determine whether the responsiveness of gustatory neurons in the nucleus tractus solitarius (NTS) is influenced by hunger, neural activity in the NTS was analyzed while monkeys were fed to satiety. Gustatory neural activity to glucose, fruit juice, NaCl, HCl and quinine HCl was measured before, while and after the monkey was fed to satiety with glucose, fruit juice or sucrose. While behavior turned from avid acceptance to active rejection upon repletion, the responsiveness of NTS neurons to the stimulus array, including the satiating solution, was unmodified. It is concluded that at the first central synapse of the taste system of the primate, neural responsiveness is not influenced by the normal transition from hunger to satiety. This is in contrast to the responses of a population of neurons recorded in the hypothalamus, which only occur to the taste of food when the monkey is hungry. Thus, NTS gustatory activity appears to occur independently of normal hunger and satiety, whereas hypothalamic neuronal activity is more closely related to the influence of motivational state on behavioral responsiveness to gustatory stimuli.     

Hunger Modulates the Responses to Gustatory Stimuli of Single Neurons in the Caudolateral Orbitofrontal Cortex of the Macaque Monkey

1. In order to determine whether the responsiveness of neurons in the caudolateral orbitofrontal cortex (a secondary cortical gustatory area) is influenced by hunger, the activity evoked by prototypical taste stimuli (glucose, NaCl, HCl, and quinine hydrochloride) and fruit juice was recorded in single neurons in this cortical area before, while, and after cynomolgous macaque monkeys were fed to satiety with glucose or fruit juice. 2. It was found that the responses of the neurons to the taste of the glucose decreased to zero while the monkey ate it to satiety during the course of which his behaviour turned from avid acceptance to active rejection. 3. This modulation of responsiveness of the gustatory responses of the neurons to satiety was not due to peripheral adaptation in the gustatory system or to altered efficacy of gustatory stimulation after satiety was reached, because modulation of neuronal responsiveness by satiety was not seen at earlier stages of the gustatory system, including the nucleus of the solitary tract, the frontal opercular taste cortex, and the insular taste cortex. 4. The decreases in the responsiveness of the neurons were relatively specific to the food with which the monkey had been fed to satiety. For example, in seven experiments in which the monkey was fed glucose solution, neuronal responsiveness decreased to the taste of the glucose but not to the taste of blackcurrant juice. Conversely, in two experiments in which the monkey was fed to satiety with fruit juice, the responses of the neurons decreased to fruit juice but not to glucose. 5. These and earlier findings lead to a proposed neurophysiological mechanism for sensory-specific satiety in which the information coded by single neurons in the gustatory system becomes more specific through the processing stages consisting of the nucleus of the solitary tract, the taste thalamus, and the frontal opercular and insular taste primary taste cortices, until neuronal responses become relatively specific for the food tasted in the caudolateral orbitofrontal cortex (secondary) taste area. Then sensory-specific satiety occurs because in this caudolateral orbitofrontal cortex taste area (but not earlier in the taste system) it is a property of the synapses that repeated stimulation results in a decreased neuronal response. 6. Evidence was obtained that gustatory processing involved in thirst also becomes interfaced to motivation in the caudolateral orbitofrontal cortex taste projection area, in that neuronal responses here to water were decreased to zero while water was drunk until satiety was produced.     

Modulation during learning of the responses of neurons in the lateral hypothalamus to the sight of food

Recordings were made from single neurons in the lateral hypothalamus and substantia innominata of the rhesus and squirrel monkey during feeding. A population of these neurons which altered their firing rates while the monkeys looked at food but not at nonfood objects was investigated. Because the responses of these neurons must have been affected by the previous experience of the animals, the activity of the neurons was measured during tasks in which the monkeys learned whether or not objects which they saw were associated with food. During visual discrimination tests these neurons came to respond when the monkey saw one stimulus associated with food (e.g., a black syringe from which the animal was fed glucose), but not when the monkey saw a different stimulus which was not associated with food (e.g., a white syringe from which the animal was offered saline). During extinction tests these units ceased to respond when the monkey saw a visual stimulus such as a peanut if the peanut was repeatedly not given to the monkey to eat. The learning or extinction behavior approximately paralleled the response of the neurons.The findings that the neurons in the lateral hypothalamus and substantia innominata respond when a monkey is shown food only if he is hungry, and as shown here, if as a result of learning the visual stimulus signifies food, provide information on a part of the brain which may be involved in feeding. The findings are consistent with other data which suggest that the responses of these neurons are involved in the autonomic and/or behavioral reactions of the animal to the sight of food.     

Sensory-specific satiety: Food-specific reduction in responsiveness of ventral forebrain neurons after feeding in the monkey

It has been shown previously that some neurons in the lateral hypothalamus and substantia innominata respond to the sight of food, others to the taste of food, and others to the sight or taste of food, in the hungry monkey. It is shown here that feeding to satiety decreases the responses of hypothalamic neurons to the sight and/or taste of a food on which the monkey has been satiated, but leaves the responses of the same neurons to other foods on which the monkey has not been satiated relatively unchanged. This suggests that the responses of these neurons in the ventral forebrain are related to sensory-specific satiety, an important phenomenon which regulates food intake. In sensory-specific satiety, the pleasantness of the sight or taste of a food becomes less after it is eaten to satiety, whereas the pleasantness of the sight or taste of other foods which have not been eaten is much less changed; correspondingly, food intake is greater if foods which have not already been eaten to satiety are offered.     

Neuronal activity in the medial orbitofrontal cortex of the behaving monkey: Modulation by glucose and satiety

To investigate neuronal responses to interoceptive information, single neuron activity of the orbitofrontal cortex (OBF) of the behaving monkey was recorded during glucose injection, natural feeding and an operant bar press feeding task. Intravenous glucose injection had almost no effect on rates of spontaneous firing, but tended to attenuate neuronal responses during the bar press and reward periods. In about half of the neurons tested, the spontaneous firing rate changed for a relatively long period after the animal ate to satiety. The results suggest that blood glucose concentration is a modulatory factor in neuronal processing for feeding, but other interoceptive information generated by satiety strongly affects the activity of OBF neurons.     

Activity of neurones in the inferotemporal cortex of the alert monkey.

The activity of neurones in the inferotemporal cortex of the alert rhesus monkey was recorded while the monkey was shown visual stimuli, which included both food and non-food objects for comparison with the activity of neurones in the lateral hypothalamus and substantia innominata. In the anteroventral part of the inferotemporal cortex, neurones were found with visual responses which were sustained while the animal looked at the appropriate visual stimuli. The latency of the responses was 100 msec or more. The majority (96/142 or 68%) of these neurones responded more strongly to some stimuli than to others. These units usually had different responses when objects were shown from different views, and physical factors such as shape, size, orientation, colour and texture appeared to account for the responses of some of these units. Association of visual stimuli with a food reward (glucose solution) or an aversive taste (5% saline solution) did not affect the magnitude of the responses of the neurones to the stimuli either during the learning or after the period of learning. Nor did feeding the monkey to satiety affect the responses of the neurones to their effective stimuli.     

Behavioral significance of monkey hypothalamic glucose-sensitive neurons

Feeding-related neuronal activity of lateral hypothalamic glucose-sensitive and glucose-insensitive neurons was investigated in behaving monkeys. The behavioral paradigm was a high fixed ratio of bar pressing for food reward signaled by light and tone cues. Twenty-seven percent of the neurons tested were glucose-sensitive. The population of neurons which changed in firing rate during the feeding task was higher among glucose-sensitive cells than among glucose-insensitive cells. The activity of many glucose-sensitive neurons decreased during the bar pressing and reward periods. A small population of glucose-sensitive neurons responded to cue stimuli. The results suggest that glucose-sensitive neurons are mainly involved in the drive and/or reward mechanism of feeding behavior, and that these cells may have specific roles in neural control of hunger-motivated food acquisition.     

Hypothalamic and zona incerta neurons in sheep, initially only responding to the sight of food, also respond to the sight of water after intracerebroventricular injection of hypertonic saline or angiotensin II

Extracellular single-unit recordings were made from neurons in the lateral hypothalamus (LH) or zona incerta (ZI) of conscious sheep. A small population of neurons (12/83) were found which responded with increased firing rate when the animal looked at food but did not respond when the sheep looked at water. The effects of rapidly inducing intense thirst by the intracerebroventricular (i.c.v.) injection of hypertonic (0.85 M) saline or 200 ng of angiotensin II, or a mixture of the two dipsogenic stimuli, on the response of neurons initially responding only to the sight of food were investigated. Following i.c.v. injection of the dipsogenic stimuli the neurons began to respond strongly to the sight of water. The results demonstrated that changing the animal's motivational state alters the response of some neurons in the LH and ZI and suggests that the neuronal response is influenced by the animal's dominant need at the time of testing.     

Complex attributes of lateral hypothalamic neurons in the regulation of feeding of alert rhesus monkeys

To elucidate the roles of glucose-sensitive (GS) and glucose-insensitive (GIS) cells of the lateral hypothalamic area (LHA), single neuron activity was recorded during 1) microelectrophoretic administration of chemicals, 2) a conditioned bar press feeding task, 3) gustatory, 4) olfactory, and 5) electrical brain stimulation. GS and GIS neurons showed different firing rate changes during phases of the task, and the responses were highly influenced by the palatability of the food and the motivational (hunger or satiety) state of the animal. The two groups of cells also differed in their responsiveness to gustatory and olfactory stimuli: GS neurons were more likely to respond to tastes and odors than GIS cells. Taste- and odor-responsive GS neurons were primarily suppressed by electrophoretically applied noradrenaline and were localized ventromedially within the LHA. The chemosensitive GIS cells, being organized along a dorsolateral axis, were especially excited by dopamine. The two sets of neurons had distinct connections with associative (orbitofrontal, prefrontal) cortical areas. GS and GIS cells, thus, appear to have differential and complex attributes in the control of feeding.     

View-responsive neurons in the primate hippocampal complex

Recordings were made from single neurons in the hippocampus and parahippocampal gyrus while macaques were moved on a platform mounted on a free-moving robot or on wheels in a cue-controlled 2 m × 2 m × 2 m environment, in order to investigate the representation of space and of spatial memory in the primate hippocampus. The test conditions allowed factors that might account for spatial firing of the cells, including the spatial location where the monkey looked, the place were the monkey was, and the head direction of the monkey, to be identified. The responses of some (“view”) neurons depended on where the monkey was looking in the enviornment, but not on the place of the monkey in the environment. The responses of one other neuron depended on a combination of where the monkey was facing and his place in the test chamber. The response of view-dependent neurons was affected by occlusion of the visual field. It was possible to show for one neuron that its “view” response rotated with rotation of the test chamber. Some neurons responded to a combination of whole-body motion and view or place, and one neuron responded in relation to whole-body movement to a particular place. One neuron responded depending on the place where the monkey was in the environment and relatively independently of view. The representations of space provided by hippocampal view-responsive neurons may be useful in forming memories of spatial environments (for example, of where an object has been seen and of where the monkey is as defined by seen views) and, together with whole-body motion cells, in remembering trajectories through environments, which is of use, for example, in short range spatial navigation. © 1995 Wiley-Liss, Inc.     

Neuronal activity in the ventral tegmental area (VTA) during motivated bar press feeding in the monkey

Neuronal activity of 58 dopaminergic (DA) and 200 non-dopaminergic (non-DA) neurons in the ventral tegmental area (VTA) of female monkeys was recorded, and correlation to bar press feeding, sensory stimulation and change in motivation was investigated. DA neurons, judged by duration of action potentials (more than 2.5 ms) and responsiveness to apomorphine, had lower firing rates (0-8 impulses/s); non-DA neurons had intermediate firing rates (10-30 impulses/s). Two-thirds of the DA and non-DA neurons responded in bar press feeding; the former with mostly tonic and the latter with phasic responses. Fifteen neurons (5%) responded phasically to arm extension toward the bar, 124 (excitation 88, inhibition 36, 45%) during bar press (BP), and 91 (excitation 32, inhibition 59, 33%) during ingestion reward (RW). Most BP responses (84/124, 68%) continued tonically throughout the BP period with no correlation to each BP movement. In 14 neurons (14/124, 11%), firing showed a specific variation: transient early BP responses shifted to tonic steady ones in palatable food trials, and the shifts correlated well with BP speed. In 20 other neurons, firing increased during BP hip lifting, and at specific vocalization to ask for food; it decreased during food ingestion, drinking and inguino-crural stimulation. Apomorphine administration decreased firing for the first 5-15 min, then increased it with frequent lip smacking, nausea, involuntary movement and vocalization. Thus VTA neurons showed mostly steady tonic responses but some specific phasic responses. They responded not only to motor events but also in close relation to changes of motivational aspects. Neuronal responses were excitation during procurement of reward and inhibition during or after perception of reward. This modulation in firing, might be important in the initiation and execution of movement and/or motivated behavior.     

Internal and external information processing by lateral hypothalamic glucose-sensitive and insensitive neurons during bar press feeding in the monkey

Single neuron activities in the lateral hypothalamic area (LHA) were recorded during bar press feeding task in the monkey. First registered neurons were sorted into 2 groups, glucose-sensitive (GS) and glucose-insensitive (GIS) neurons, depending on their glucose sensitivity. Then firing variations to feeding, electrophoretically applied catecholamines and opiate, and to odor and taste stimuli were investigated. GS neurons responded to dopamine, noradrenaline and morphine more often than GIS neurons. In feeding task GS neurons responded during bar press (BP) and reward (RW) periods with long-lasting inhibition of firing and at cue tone (CT) with transient inhibition, while GIS neurons responded during BP and RW periods mainly with excitation and at cue light (CL) with excitation. A majority of GS neurons responded to both odor and taste stimuli more often than GIS neurons. Data suggest that these two kinds of neurons in the LHA may be involved in different functional aspects of feeding: GS neurons, mainly in internal information processing and reward mechanism, and GIS neurons, in external information processing and motor aspects.     

Dopaminergic unit activity in freely moving cats: Lack of relationship to feeding, satiety, and glucose injections

The activity of dopaminergic neurons in the substantia nigra was recorded from freely moving cats during feeding and satiety, and following injections of glucose. At no time during feeding or in the postprandial satiety period was there a significant increase or decrease in firing rate of these neurons relative to baseline. Additionally, no change in firing rate was observed following injections of glucose (300, 500 and 1000 mg/kg) or glucose in combination with insulin (300 mg/kg glucose and 0.8 units/kg insulin).     

Role of monkey hippocampus in recognition of food and nonfood

To investigate the role of the hippocampal formation (HF) in feeding behavior, single neuron activity in the monkey HF was recorded during performance of an operant task that included food/nonfood discrimination, drinking, and active avoidance. Of 837 neurons recorded in the HF, 155 responded to the sight of one or more objects. Of these, 82 responded to the sight of different objects with different response magnitudes, and some of these 82 responded predominantly to food-related (rewarding) objects or nonfood, aversive objects. The magnitude of response of neurons that responded predominantly to food was not necessarily correlated with the order of animal's preference for those kinds of food. For some neurons that responded predominantly to food or nonfood, effects of extinction or reversal learning on the neuronal responses were tested, and most of the neurons tested maintained their original responsiveness even after behavioral extinction or reversal learning was accomplished. The results suggest that these HF neurons may be involved in preservation of past information concerning food or nonfood.     

Spatial- and task-dependent neuronal responses during real and virtual translocation in the monkey hippocampal formation.

Neuropsychological data in humans demonstrated a pivotal role of the medial temporal lobe, including the hippocampal formation (HF) and the parahippocampal gyrus (PH), in allocentric (environment-centered) spatial learning and memory. In the present study, the functional significance of the monkey HF and PH neurons in allocentric spatial processing was analyzed during performance of the spatial tasks. In the tasks, the monkey either freely moved to one of four reward areas in the experimental field by driving a cab that the monkey rode (real translocation task) or freely moved a pointer to one of four reward areas on the monitor (virtual translocation task) by manipulating a joystick. Of 389 neurons recorded from the monkey HF and PH, 166 had place fields that displayed increased activity in a specific area in the experimental field and/or on the monitor (location-differential neurons). More HF and PH neurons responded in the real translocation task. These neurons had low mean spontaneous firing rates (0.96 spikes/sec), similar to those of rodent HF place cells. The remaining nonresponsive neurons had significantly higher mean firing rates (8. 39 spikes/sec), similar to interneurons or theta cells in the rodent HF. Furthermore, most location-differential neurons showed different responses in different tasks. These results suggest that the HF and PH are crucial in allocentric information processing and, moreover, that the HF can encode different reference frames that are context or task-dependent. This may be the neural basis of episodic memory.     

Thermal, osmotic and chemical modulation of neural activity in the paraventricular nucleus: In vitro studies

To investigate the functions of the paraventricular nucleus (PVN) which plays an important role as an integration site for the neuroendocrine and autonomic nervous systems, the firing activity of PVN neurons was recorded from hypothalamic slice preparations during thermal, osmotic and chemical stimulation. Neurons responded to environmental factors such as temperature and osmolarity and both warm-responsive and cold-responsive neurons were observed in the PVN. Some PVN neurons were also osmoresponsive and unlike neurons in the supraoptic nucleus, most osmoresponsive PVN neurons decreased their firing rate during hyperosmotic stimulation. One of the classical transmitters, noradrenaline, exerted excitatory effects on PVN neurons through ₁- and β-receptors and inhibitory responses through ₂-receptors. Atrial natriuretic polypeptide exerted inhibitory effects on putative parvocellular PVN neurons but it had no effect on putative magnocellular PVN neurons. An endogenous sugar derivative, 2-deoxytetronic acid, thought to be an endogenous satiety factor, elicited inhibitory effects, supporting the possibility that the PVN also may be related to feeding behaviour. Arginine-vasopressin and oxytocin which are synthesised in the magnocellular neurosecretory cells excited PVN neurons, suggesting that the PVN may have short circuits modulating neural activity within the nucleus itself. We conclude that neurons in the PVN may receive multiple information and act as one of the important integrative sites in the brain.     

Anatomical distribution and sensory properties of brain stem and posterior diencephalic neurons responding to genital, somatosensory, and nociceptive stimulation in the squirrel monkey.

In chloralose-urethane-anesthetized female squirrel monkeys, 325 single units sampled from a region extending from the caudal medulla to the posterior diencephalon were examined for responsiveness to genital, rectal, innocuous somatosensory, and various forms of nociceptive stimulation. The units were highly responsive, with 84% responding to at least one stimulus type. The responsive units were widely distributed in the brain stem tegmentum, deep tectum, and posterior diencephalon. Very few neurons responded to only one type of stimulation. The patterns of convergent responsiveness to the various stimulus types were not, however, a simple random function of unit responsiveness to each type of stimulus per se. Unit responses to vaginal stimulation consisted of simple increases or decreases in firing which outlasted the duration of the probing stimulus in most cases. Some units responded more strongly to cervical than to vaginal tract stimuli. The somatic receptive fields of units responding to touch-pressure stimuli were typically bilateral and quite extensive. A forceps pinch of nociceptive intensity elicited a response from 64% of the cells, and of these, 11% showed significant linear correlations between their firing rates and increasing pinch pressure in the nociceptive intensity range. Brief, localized nociceptive thermal stimuli and needle pricks failed to elicit responses from the neurons tested. Based on a comparison between the response properties of monkey brain stem neurons and the previous findings for rat and cat neurons, it was concluded that brain stem cells display species-typical sensory characteristics which have parallels in the properties of behavioral responses of these three species to genital and other sensory stimuli. Properties of unit responses to nociceptive stimuli have implications in relation to the neural mechanisms of first and second pain.     

Neuronal responses in monkey lateral hypothalamus during operant feeding behavior

Single neuron activity was recorded from monkey lateral hypothalamus to investigate neuronal events correlated with operant bar press feeding behavior. The behavioral paradigm was divided into three phase: visual (discrimination), bar press (procurement), and ingestion (consummatory). Of 669 neurons tested, 158 (24%) responded in one or more phases. During the visual phase, 106 neurons (16%) responded. Of 80 neurons that responded in the visual phase and were tested systematically, 33 (41%, 33/80) responded selectively to the sight of food or nonfood objects associated with a juice reward, but not to the sight of nonfood or objects associated with aversive saline. Neuronal activity related to discrimination was modulated by satiation and learning (i.e., acquisition and extinction). During the bar press phase, 51 neurons (7.6%) responded. These responded tonically during the early or late stage of the bar press period, but did not depend on individual bar pressing motions. During ingestion, 90 neurons (13%) responded. The ingestion response was modulated by palatability of food and satiation. Data suggest that the LHA is deeply involved in operant feeding behavior; discrimination of food, drive to get food, and perception of reward, all of which are affected by learning and internal states such as hunger and satiety.     

Catecholaminergic mechanisms of feeding-related lateral hypothalamic activity in the monkey

The functional role of the catecholaminergic mechanism in the lateral hypothalamus (LHA), in feeding behavior of the monkey was investigated by single neuron activity recording and electrophoretic application of dopamine (DA), noradrenaline (NA) and their antagonists. The feeding paradigm had 4 phases: cue light (CL) signaled start of bar press; bar press (BP, 20-30 times); short cue tone (CT) triggered by last bar press signaled presentation of food; and ingestion-reward (RW). Of 312 neurons tested, 189 (61%) responded in one or more phases of the feeding task. Two types of response were observed: CL- or CT-related transient, and BP- or RW-related long-lasting responses. These feeding-related responses depended on the nature of the food and on the hunger-satiety level. DA excited or inhibited different neurons, while NA mainly inhibited firing. DA-sensitive neurons responded more often in the feeding task than insensitive neurons due mainly to differences in responsiveness to CL on (chi 2 test, P less than 0.01), at motor initiation, and during BP (P less than 0.05). Spiperone blocked the former two responses. NA-sensitive neurons responded more often in the feeding task due to responsiveness during BP and RW (P less than 0.01). Sotalol blocked some BP-related responses, and phenoxybenzamine and sotalol blocked the CT-related responses. The data suggest that dopaminergic and noradrenergic inputs in the LHA are crucial in task initiation and reward processing, respectively. Integration of these catecholaminergic and other inputs in the LHA might be important in accomplishing motivated feeding.     

Deletion of TASK1 and TASK3 channels disrupts intrinsic excitability but does not abolish glucose or pH responses of orexin/hypocretin neurons

The firing of hypothalamic hypocretin/orexin neurons is vital for normal sleep–wake transitions, but its molecular determinants are not well understood. It was recently proposed that TASK (TWIK-related acid-sensitive potassium) channels [TASK1 (K_2P3.1) and/or TASK3 (K_2P9.1)] regulate neuronal firing and may contribute to the specialized responses of orexin neurons to glucose and pH. Here we tested these theories by performing patch-clamp recordings from orexin neurons directly identified by targeted green fluorescent protein labelling in brain slices from TASK1/3 double-knockout mice. The deletion of TASK1/3 channels significantly reduced the ability of orexin cells to generate high-frequency firing. Consistent with reduced excitability, individual action potentials from knockout cells had lower rates of rise, higher thresholds and more depolarized after-hyperpolarizations. However, orexin neurons from TASK1/3 knockout mice retained typical responses to glucose and pH, and the knockout animals showed normal food-anticipatory locomotor activity. Our results support a novel role for TASK genes in enhancing neuronal excitability and promoting high-frequency firing, but suggest that TASK1/3 subunits are not essential for orexin cell responses to glucose and pH.